Advancing sex and gender research in dementia

By Lauren Bentley

Sex and gender differences matter when it comes to improving outcomes for dementia. These postdoctural fellows are showing us how.

In early 2024, two outstanding trainees in brain health research—Dr. Natasha Clarke and Dr. Rikki Lissaman—each received a postdoctoral fellowship of $60,000 a year for two years through the Canadian Consortium on Neurodegeneration in Aging (CCNA) Phase II Women, Sex and Gender in Dementia (WSGD) cross-cutting program (now called the Sex and Gender Hub). They are two of the four trainees to receive the award that Brain Canada helped fund as a proud partner of the CCNA, a pan-Canadian collaborative effort making strides in our understanding and treatment of dementia. 

Despite progress in this area, research on aging and neurodegeneration does not always account for sex and gender differences. Sex refers to a set of physical and physiological features in humans and animal models, while gender refers to the socially constructed roles, behaviours, expressions, and identities of individuals. The WSGD program helps fill a critical gap by allowing researchers to amplify their focus in this area and help advance more equitable and effective research outcomes.  

By investing in promising trainees at the postdoctoral level, this fellowship helps build research capacity from the cellular/molecular to population health while augmenting Canada’s contribution to understanding the role of sex and gender in brain health and aging. Advancing critical knowledge about aging and the brain sets the stage for better outcomes and more personalized treatments for Canadians in the years to come. 

Dr. Natasha Clarke, Postdoctoral Research Associate at Université de Montréal 

“Speech is so rich. It can tell us so much about a person’s brain or cognitive state,” says Dr. Natasha Clarke.  

Dr. Clarke, under the supervision of Dr. Simona Maria Brambati, studies the relationship between speech and aging, an area of curiosity that developed during her years as a clinician working with patients experiencing memory loss.  

Through her work, she studies how changes in connected speech, the natural, free-flowing conversations most of us have every day, can reveal very early signs of dementia, often years before other, more well-recognized symptoms emerge, such as memory problems. Her hope is to find potential biomarkers in speech that might identify disease earlier and allow clinicians to track disease progression much less invasively than traditional tests.  

The CCNA WSGD Postdoctoral Fellowship, with the support of Brain Canada, has enabled Dr. Clarke to bring a focus on sex and gender differences to her research. For example, women often do better on verbal memory tests, which can delay diagnosis. She’s exploring whether connected speech shows similar differences. Dr. Clarke’s early work suggests that there are likely meaningful differences in men and women when it comes to connected speech. Understanding these differences could go a long way in improving diagnostic tools and building more personalized interventions.  

“Bringing in a sex and gender focus is hugely important,” she notes.

“It’s wonderful to see more and more emphasis being put on it now, especially since women and men go through such different changes throughout life.” 

Dr. Clarke is also using fMRI to link changes in speech with changes in brain function, which may help guide earlier treatments. Using COMPASS-ND, a massive CCNA-provided dataset with longitudinal samples from thousands of Canadians, she and the Dr. Brambati’s team can look more closely at these questions than ever before. 

Dr. Clarke’s supervisor, Professor Maria Brambati, was delighted to learn her trainee had received the fellowship. “Natasha is an outstanding postdoctoral researcher, deeply committed to equity in scientific research,” she said. “Her research program carries a long-term mission to help build a more inclusive society—particularly through the development of technological solutions, health innovations, and equitable access to care. These values are strongly shared between her and the laboratory. I’m grateful to the WSGD of the CCNA for encouraging and supporting this important work.” 

“I was completely over the moon when I received this funding,” Dr. Clarke says. “It was amazing to know I had two years to further my work.” She notes how validating it was for CCNA to recognize the importance and potential of her research questions for everyday Canadians facing neurodegeneration. 

Dr. Rikki Lissaman, Postdoctoral Fellow at Toronto Metropolitan University 

Dr. Rikki Lissaman has been studying the gene APOE since he was an undergraduate student. It’s a gene we all have, but for people with two copies of the APOE4 variant of the gene, the risks of getting Alzheimer’s disease rise significantly. This type of correlation between a normal gene variant and increased disease risk is quite rare, making the gene a key path of inquiry for studying Alzheimer’s.  

In his current work, Dr. Lissaman is exploring whether it’s possible to detect the impact of APOE4 as early as midlife, especially in females, before more typical Alzheimer’s symptoms tend to appear. 

Using diffusion-weighted imaging and fMRI, Dr. Lissaman studies how the brain responds as females and males perform various memory tasks. By looking at a diverse group of people, across sexes and genotypes, his work is contributing to our understanding of what distinguishes standard from pathological aging and why some people age with healthier brains than others.  

He is also looking at the role that sex plays in aging, which he can explore more deeply thanks to this fellowship. He is interested in how menopause and other hormonal changes affect how the brain ages over time, particularly in midlife, when male and female cognitive aging patterns may start to diverge. 

In the long term, Dr. Lissaman envisions his efforts supporting earlier, more personalized strategies for helping people maintain cognitive and brain health later in life. 

“The fellowship has been a great opportunity to not just deepen my interest in Alzheimer’s disease risk and aging but also tie in this crucial angle of sex and gender,” he says. “This work will allow us to better understand the role that the APOE4 genetic risk factor has, while opening up the potential for interventions that are more tailored to each individual.” 

Dr. Lissaman notes that sex and gender differences in aging are still understudied. His supervisor at Toronto Metropolitan University, Dr. Natasha Rajah, Principal Investigator at the BHEAM Lab, agrees.  

“The CCNA WSGD Postdoctoral Fellowship is essential for supporting promising researchers like Dr. Rikki Lissaman to pursue questions around sex and gender, which is often neglected in this space,” she says. “Dr. Lissaman’s preliminary findings are exciting and help advance our understanding of why females may be at more risk of Alzheimer’s disease than males.” 

“There’s still work to be done,” he says.

“It’s so important that there are opportunities like this for trainees. And the more funding bodies that take the lead, like CCNA and Brain Canada have, can only have positive outcomes.” 

One year into his fellowship, Dr. Lissaman moved to a new role at Royal Holloway, University of London, where he is continuing to explore the same research questions.